This project is comprised of three major areas of work: selection of screening leads for preliminary investigation by LDDRD staff, dereplication of those leads for compounds of known structure and antitumor or anti-HIV activity, and identification and prioritization of extracts which survive the dereplication process, i.e., those extracts most likely to contain novel chemotypes with antitumor or HIV-inhibitory activity. These areas of effort are closely linked, providing a logical sequence of steps designed (and continuously refined) to direct the available resources of LDDRD to those leads with the greatest potential for the DTP drug discovery and preclinical development effort. The primary focus in this project lies in the dereplication and chemical screening of those initial leads. The objective is to obtain the maximum amount of information regarding the chemical composition of the active constituents of each extract lead with the least amount of time, effort, expense and screening capacity. The goals are to identify (and thus eliminate) those extracts for which bioactivity is most probably due to already known compounds or compound classes and to develop a chemical screen profile (a chromatography elution pattern) for extracts most likely to contain new potential antitumor and anti-HIV chemotypes.